TY - JOUR
T1 - Pathways to clinical CLARITY
T2 - Volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
AU - Hsueh, Brian
AU - Burns, Vanessa M.
AU - Pauerstein, Philip
AU - Holzem, Katherine
AU - Ye, Li
AU - Engberg, Kristin
AU - Wang, Ai Chi
AU - Gu, Xueying
AU - Chakravarthy, Harini
AU - Arda, H. Efsun
AU - Charville, Gregory
AU - Vogel, Hannes
AU - Efimov, Igor R.
AU - Kim, Seung
AU - Deisseroth, Karl
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.
AB - Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.
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U2 - 10.1038/s41598-017-05614-4
DO - 10.1038/s41598-017-05614-4
M3 - Article
C2 - 28724969
AN - SCOPUS:85025664400
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 5899
ER -